The major objective and long-range goal of this research program is an increased understanding of the normal metabolism of the visual cells in the vertebrate retina. The proposed research is designed to yield new information concerning the chemical reactions in the cell nucleus, with particular attention to the DNA, histones, and non-histone chromosomal proteins (NHCP). One project deals with the cycles of cell division which occur just prior to differentiation of the visual cells in the developing retina. The timing of the various phases of the cell cycle will be analyzed, to determine the intermittent or variable rates of synthesis of DNA, RNA, histone, and NHCP. Post-synthetic modification of the chromatin proteins by acetylation and phosphorylation will also be examined. Another aspect of the proposed investigations concerns changes in the structure and metabolism of the nuclear chromatin during the period of visual cell differentiation. A further point of emphasis is the question of the stability or renewal of chromosomal constituents, analyzed by determining the rate of loss of radioactive labeling after synthesis in the presence of a radioactive precursor. Finally, the capacity of visual cells to repair molecular damage to the DNA or proteins of their chromosomes will be examined, including the question of whether such damage and repair can be provoked by radiation present in the normal energy environment. The major methods to be used are histochemistry, light and electron microscopy, autoradiography, and radiobiochemistry.